Safer Conception Among HIV-1 Sero-Discordant Couples in East Africa: Understanding Knowledge, Attitudes, and Experiences

Thesis (Master's)--University of Washington, 2016-06Context: Supporting people affected by HIV-1 in achieving their reproductive goals while minimizing the risk of HIV-1 transmission is a public health imperative. Background: For HIV-1 serodiscordant couples, HIV-1 exposure and risk of transmission to the uninfected partner and unborn children is heightened during pregnancy attempts but safer conception strategies can mitigate risk. Understanding couples’ choices and experiences with safer conception can be useful for programmatic recommendations as safer conception programs are scaled up. Methods: 1013 high-risk, heterosexual HIV-1 serodiscordant couples from Kenya and Uganda were followed for two years in an open-label delivery study of integrated pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART), the Partners Demonstration Project. Annually, we assessed participant experience with safer conception strategies. Multivariate logistic regression was used to characterize women who reported ever having used a safer conception strategy during their first annual visit. Results: 859 couples were included in analysis. 66% of couples had HIV-infected women and 86% desired future children. The median age for women was 27 (interquartile range: 23-32). At the first annual visit, 32% of women reported use of a safer conception strategy ever in their life: 14% reported using ART, 16% PrEP, 3% self-insemination, and 2% STI treatment. Women who reported discussing their fertility desires with their male partners (adjusted odds ratio (aOR) = 1.91, 95% confidence interval (CI) 1.26-2.589), had no living children at the time of study enrollment (aOR = 1.71, 95% CI 1.14-2.57), and were HIV-uninfected (aOR = 1.56, 95% CI 1.11-2.20) were more likely to report having used at least one safer conception strategy. Conclusions: HIV-1 prevention counseling for serodiscordant couples should integrate opportunities for couples to share their fertility desires and discuss preferences for safer conception strategies

The Expansion of Body Coloration Involves Coordinated Evolution in cis and trans within the Pigmentation Regulatory Network of Drosophila prostipennis

The generation of complex morphological features requires the precisely orchestrated expression of numerous genes during development. While several traits have been resolved to evolutionary changes within a single gene, the evolutionary path by which genes derive co-localized or mutually excluded expression patterns is currently a mystery. Here we investigate how the Drosophila pigmentation gene network was altered in Drosophila prostipennis, a species in the Drosophila melanogaster subgroup, that evolved expanded abdominal pigmentation. We show that this expansion involved broadened expression of the melanin-promoting enzyme genes tan and yellow, and a reciprocal withdrawn pattern of the melanin-suppressing enzyme gene ebony. To examine whether these coordinated changes to the network were generated through mutations in the cis-regulatory elements (CREs) of these genes, we cloned and tested CREs of D. prostipennis tan, ebony, and yellow in transgenic reporter assays. Regulatory regions of both tan and ebony failed to recapitulate the derived D. prostipennis expression phenotype, implicating the modification of a factor or factors upstream of both genes. However, the D. prostipennis yellow cis-regulatory region recapitulated the expanded expression pattern observed in this species, implicating causative mutations in cis to yellow. Our results provide an example in which a coordinated expression program evolved through independent changes at multiple loci, rather than through changes to a single “master regulator” directing a suite of downstream target genes. This implies a complex network structure in which each gene may be subject to a unique set of inputs, and resultantly may require individualized evolutionary paths to yield correlated gene expression patterns

Informed Consent for a Neonatal Clinical Trial: Parental Experiences and Perspectives

OBJECTIVE: There is a variability regarding timing of consent and personnel used in patient recruitment for neonatal research. We explored the associations between the study personnel and timing of consent with parents\u27 decisional conflict and ultimately their decision to enroll. STUDY DESIGN: This was a multi-site, cross-sectional survey conducted between August 2015 and October 2017. Participants were parents approached to enroll their 24-28-week infant in a clinical trial. Parents completed an interviewer-administered 61-item questionnaire. RESULTS: Overall, 163 surveys were completed; 105 by parents of enrolled infants and 58 by parents of non-enrolled infants (54.5% participation rate). Neither the individual requesting nor timing of consent was associated with parents\u27 knowledge score, decisional conflict, or decision to enroll. Parents preferred to be approached prenatally and by their infant\u27s doctor. CONCLUSION: Study designers and IRBs may allow flexibility in personnel and timing of consent as it is respectful of parents and may enhance trial enrollment